PCSK9 Plasma Concentrations Are Independent of GFR and Do Not Predict Cardiovascular Events in Patients with Decreased GFR

PLoS One. 2016 Jan 22;11(1):e0146920. doi: 10.1371/journal.pone.0146920. eCollection 2016.

Abstract

Background: Impaired renal function causes dyslipidemia that contributes to elevated cardiovascular risk in patients with chronic kidney disease (CKD). The proprotein convertase subtilisin/kexin type 9 (PCSK9) is a regulator of the LDL receptor and plasma cholesterol concentrations. Its relationship to kidney function and cardiovascular events in patients with reduced glomerular filtration rate (GFR) has not been explored.

Methods: Lipid parameters including PCSK9 were measured in two independent cohorts. CARE FOR HOMe (Cardiovascular and Renal Outcome in CKD 2-4 Patients-The Forth Homburg evaluation) enrolled 443 patients with reduced GFR (between 90 and 15 ml/min/1.73 m2) referred for nephrological care that were prospectively followed for the occurrence of a composite cardiovascular endpoint. As a replication cohort, PCSK9 was quantitated in 1450 patients with GFR between 90 and 15 ml/min/1.73 m2 enrolled in the Ludwigshafen Risk and Cardiovascular Health Study (LURIC) that were prospectively followed for cardiovascular deaths.

Results: PCSK9 concentrations did not correlate with baseline GFR (CARE FOR HOMe: r = -0.034; p = 0.479; LURIC: r = -0.017; p = 0.512). 91 patients in CARE FOR HOMe and 335 patients in LURIC reached an endpoint during a median follow-up of 3.0 [1.8-4.1] years and 10.0 [7.3-10.6] years, respectively. Kaplan-Meier analyses showed that PCSK9 concentrations did not predict cardiovascular events in either cohort [CARE FOR HOMe (p = 0.622); LURIC (p = 0.729)]. Sensitivity analyses according to statin intake yielded similar results.

Conclusion: In two well characterized independent cohort studies, PCSK9 plasma levels did not correlate with kidney function. Furthermore, PCSK9 plasma concentrations were not associated with cardiovascular events in patients with reduced renal function.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Biomarkers / blood*
  • Cardiovascular Diseases / blood
  • Cardiovascular Diseases / etiology*
  • Cardiovascular Diseases / pathology
  • Female
  • Follow-Up Studies
  • Glomerular Filtration Rate*
  • Humans
  • Kidney Failure, Chronic / complications
  • Kidney Failure, Chronic / surgery*
  • Kidney Function Tests
  • Kidney Transplantation / adverse effects*
  • Male
  • Middle Aged
  • Postoperative Complications*
  • Prognosis
  • Proprotein Convertase 9
  • Proprotein Convertases / blood*
  • Prospective Studies
  • Risk Factors
  • Serine Endopeptidases / blood*

Substances

  • Biomarkers
  • PCSK9 protein, human
  • Proprotein Convertase 9
  • Proprotein Convertases
  • Serine Endopeptidases

Grant support

The CARE FOR HOMe study was supported by a grant from the Else Kröner-Fresenius Stiftung. PCSK9 analyses in CARE FOR HOMe were funded by a grant from the Dr. Marija Orlovic Stiftung awarded to Christian Werner. The LURIC study was supported by a grant from the Jubiläumsfond der Oesterreichischen Nationalbank (No. 14219 to H.S.). WM is employed at synlab Services GmbH, Augsburg, Germany, as a board licensed specialist for laboratory medicine. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.